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Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy
Author(s) -
Pernot Fabien,
Heinrich Christophe,
Barbier Laure,
Peinnequin André,
Carpentier Pierre,
Dhote Franck,
Baille Valérie,
Beaup Claire,
Depaulis Antoine,
Dorandeu Frédéric
Publication year - 2011
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2011.03273.x
Subject(s) - epileptogenesis , status epilepticus , kainate receptor , epilepsy , glial fibrillary acidic protein , biology , neuroinflammation , microglia , kainic acid , neuroscience , endocrinology , medicine , immunology , glutamate receptor , receptor , inflammation , ampa receptor , immunohistochemistry , biochemistry
Summary Purpose: Neuroinflammation appears as a prominent feature of the mesiotemporal lobe epilepsy syndrome (MTLE) that is observed in human patients and animal models. However, the precise temporal relationship of its development during epileptogenesis remains to be determined. The aim of the present study was to investigate (1) the time course and spatial distribution of neuronal death associated with seizure development, (2) the time course of microglia and astrocyte activation, and (3) the kinetics of induction of mRNAs from neuroinflammatory‐related proteins during the emergence of recurrent seizures. Methods: Experimental MTLE was induced by the unilateral intrahippocampal injection of kainate in C57BL/6 adult mice. Microglial and astrocytic changes in both ipsilateral and contralateral hippocampi were examined by respectively analyzing griffonia simplicifolia (GSA) lectin staining and glial fibrillary acidic protein (GFAP) immunoreactivity. Changes in mRNA levels of selected genes of cytokine and cytokine regulatory proteins (interleukin‐1β, IL‐1β; interleukin‐1 receptor antagonist, IL‐1Ra; suppressor of cytokine signaling 3, SOCS3) and enzymes of the eicosanoid pathway (group IVA cytosolic phospholipase A2, cPLA 2 ‐α; cycloxygenase‐2, COX‐2) were studied by reverse transcription‐quantitative real time polymerase chain reaction. Key Findings: Our data show an immediate cell death occurring in the kainate‐injected hippocampus during the initial status epilepticus (SE). A rapid increase of activated lectin‐positive cells and GFAP‐immunoreactivity was subsequently detected in the ipsilateral hippocampus. In the same structure, Il‐1β, IL‐1Ra, and COX‐2 mRNA were specifically increased during SE and epileptogenesis with a different time course. Conversely, the expression of SOCS3 mRNA, a surrogate marker of interleukin signaling, was mainly increased in the contralateral hippocampus after SE. Significance: Our data show that specific neuroinflammatory pathways are activated in a time‐ and structure‐dependent manner with putative distinct roles in epileptogenesis.